Early peripheral T-cell immune dynamics during anti-PD-1 therapy as potential biomarkers of treatment response in metastatic non-small cell lung cancer: a prospective pilot study

Abstract

Introduction : Reliable peripheral immune biomarkers for monitoring response to anti-PD-1 therapy in metastatic NSCLC remain poorly defined. Dynamic changes within circulating T-cell compartments may reflect early pharmacodynamic immune remodeling associated with treatment response. Aim : To evaluate early peripheral T-cell immune dynamics during anti-PD-1 therapy and explore their potential as biomarkers of radiologic response. Materials and methods : Prospective paired peripheral blood immune profiling was performed in patients with metastatic NSCLC treated with pembrolizumab-based combination immunochemotherapy at baseline and after completion of four treatment cycles. Multicolor flow cytometry was used to assess T-cell activation (CD69), co-stimulatory competence (CD8⁺ CD28⁺), and regulatory T cells (Treg). Baseline-to-cycle-4 changes were analyzed descriptively and compared according to radiologic response. Results : Four patients with paired immune assessments were included. Two achieved partial response (PR) and two had stable disease (SD). Early peripheral immune remodeling was observed across patients, characterized by decreased CD4⁺ CD69⁺ and CD8⁺ CD69⁺ T cells and increased Treg frequencies. A consistent increase in CD8⁺ CD28⁺ T cells was observed in PR patients, whereas SD patients demonstrated heterogeneous changes. These findings suggest differential early modulation of CD8⁺ co-stimulatory capacity according to treatment response. Conclusions : Early peripheral T-cell immune dynamics during pembrolizumab-based immunochemotherapy may reflect biologically relevant immune remodeling associated with radiologic response. Serial flow-cytometric monitoring of CD8⁺ CD28⁺ T cells may represent a promising candidate peripheral biomarker and warrants further investigation in larger cohorts.